Abstract
Background: Idiopathic interstitial pneumonia is characterized by fibroblast proliferation and extracellular matrix (ECM) accumulation. Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have been shown to regulate remodeling of the ECM, which indicates that they are important factors in the process of lung fibrosis. Therefore, we evaluated the expression of MMPs and TIMPs in tissues obtained from patients with idiopathic interstitial pneumonia and control tissues. Methods: Thirty-seven patients who were diagnosed with IIP (22: IPF, 13: NSIP, 2: COP) and 5 controls were enrolled in this study. The MMP-2 and -9 activity in lung tissue obtained from these patients was analyzed using gelatin zymography and the levels of TIMP-1 and -2 were measured by western blotting. We also evaluated the expression of MMP-2 and -9, as well as that of TIMP-1 and -2 in lung tissue using immunohistochemistry. Results: The levels of MMP-2 and MMP-9 were significantly increased in patients with IPF compared to those with NSIP and COP. The activities of TIMP-1 and -2 were also higher in patients with IPF than NSIP/COP patients and control subjects. There were no significant differences observed in the activities of MMPs and TIMPs obtained from patients with NSIP/COP and control subjects. The immunohistochemical analysis showed that TIMP-2 and MMP-2 were strongly stained at the fibroblasts of the fibroblastic foci in patients with IPF. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma.
Highlights
Idiopathic interstitial pneumonia (IIP) is comprised of a group of interstitial pneumonias of unknown etiology that is divided into seven disease entities, including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP), on the basis of clinical, radiological and pathological findings [1]
It is well known that the activities of tissue inhibitors of metalloproteases (TIMPs) and gelatinases are high in patients with IPF, it is still unclear if the expression of Matrix metalloproteases (MMPs) and TIMPs in cases of IIP is associated with a favorable prognosis, such as occurring in cases of NSIP and COP
We evaluated the activities of MMP-2 and -9, as well as those of TIMP-1 and -2 using lung tissue obtained from patients with IPF, NSIP and COP
Summary
Idiopathic interstitial pneumonia (IIP) is comprised of a group of interstitial pneumonias of unknown etiology that is divided into seven disease entities, including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP), on the basis of clinical, radiological and pathological findings [1]. MMPs are proteolytic enzymes known to regulate the extracellular matrix (ECM) turnover, it has been suggested that they play an important role in lung diseases associated with tissue remodeling [7] [8]. It has been suggested that, in cases of IPF, over-expression of TIMP inhibits degradation of the extracellular matrix (ECM), which induces excess deposition of ECM [6] Gelatinases, such as MMP-2 and -9, might play an important role in the disruption of the basement membrane, which in turn induce migration of the fibroblasts [6]. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma
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